Immunotherapeutics firm Coronado Biosciences sealed a collaboration agreement with Dr. Falk Pharma and OvaMed, relating to the development and commercialization of TSO (Trichuris suis ova; CNDO-201) for the treatment of Crohn disease. The porcine whipworm eggs are manufactured by OvaMed. Under terms of the latest agreement deal Coronado has licensed the orally administered immunomodulator from OvaMed for development in North America, South America, and Japan. Dr. Falk’s license from OvaMed covers gastroenterology applications of the candidate in Europe.

As part of the collaboration Dr. Falk has granted Coronado exclusive rights and licenses to certain preclinical and clinical data from studies of TSO in Crohn disease, including an ongoing Phase II study, for use by the latter in its designated territories. In return, Dr. Falk gets exclusive rights and licenses to data from Coronado’s clinical trials of TSO in Crohn disease for use in Europe. Coronado will pay Dr. Falk €500 million once it has received specified data, and a royalty of 1% of net sales of TSO.

The two firms will each be responsible for carrying out clinical trials on half the total number of patients needed to achieve regulatory clarance of TSO for the Crohn disease indication in the U.S. and Europe. Certain preclinical development costs will also be shared.

In January 2011 Coronado acquired assets from Asphelia Pharmaceuticals relating to CNDO-201, as a potential immunotherapy for the treatment of Crohn disease, ulcerative colitis, multiple sclerosis, and other autoimmune disorders. The assets include exclusive rights to CNDO-201 in North America, South America, and Japan, under a sublicense agreement with OvaMed.

The use of helminths as a treatment for autoimmune disease is based on the Hygiene Hypothesis, which suggests that the immune systems of populations living in the relatively sterile, parasite-free environments of developed and temperate countries may not develop normally. Indeed, Coronado points out, the incidence of most autoimmune diseases is highest in the developed world and in temperate climates, and particularly among people of the highest socioeconomic statuses and levels of domestic hygiene in childhood. Conversely, the incidence of, for example, inflammatory bowel disease (IBD), is rare in less developed countries and among manual workers exposed to dirt and physical exercise.

These epidemiological findings have led to the notion the elimination of intestinal helminths in the industrialized world has basically led to inactivation of a natural T-regulatory-cell mechanism that would naturally act to prevent excessive T-cell activation. This inactivation occurs in IBD and other immune-mediated diseases such as multiple sclerosis, type-1 diabetes, asthma, and allergies.

Experimental findings have indicated that a number of helminths induce Th2-type cytokine release and downregulate the Th1 immune responses to unrelated bacterial and viral infections. So, the theory goes, colonization with intestinal helminths might be beneficial in reducing inflammation in patients with IBD, multiple sclerosis, and other autoimmune diseases. “Epidemiologic evidence, case control observations, animal studies, and clinical studies all suggest that helminths may afford protection from or even treat autoimmune diseases,” Coronado states.

TSO has been selected as a clinical candidate because as a nonhuman parasite, it is naturally eliminated from the body within a few weeks. Conorado says multiple investigator-sponsored clinical trials evaluating TSO for the treatment of Crohn disease, ulcerative colitis, and multiple sclerosis have already been completed and demonstrated that the porcine helminth egg therapy results in meaningful clinical benefit.